The invention relates to micro sized pumps which transport chemicals on micro sized devices for chemical analysis on such devices and to micro sized chemical analysis systems utilizing such pumps. Typically, the pumps are formed on silicon chips.
Advances in micromachining techniques have enabled the mass production of miniature and microscopic electromechanical components that perform a variety of functions. These components fall generally into two categories: sensors and actuators. Sensors can be made to monitor measurands such as pressure, acceleration, chemical-vapor concentrations, light intensity and magnetic fields. Actuators include pumps and valves for fluid manipulation, heated chambers to induce chemical reactions, moveable mirrors for optical displays and relay switches for high-frequency communications.
In addition to direct miniaturization and mass production, a feature of micromachining is that it enables the implementation of new types of technologies. With miniaturization, physical laws of scaling inherently favor certain technologies and phenomena over others. In some cases, technologies that can be made by micromachining work well on the microscopic scale but have no analogy or usefulness in the macroscopic domain (e.g., the electrostatic micromotor).
The ultimate power of microfabrication lies in the ability to integrate multiple components into complex microelectromechanical systems (MEMS) that have high functionality and performance, yet are small, easy to use and to produce, and inexpensive. An example of a complex microelectromechanical system is the digital micromirror display marketed by Texas Instruments, based on an array of a plurality of individually-addressable micromirrors.
One of the attributes of these systems is that they can be made fully self-contained and can be operated remotely without direct user intervention for sample handling or other tasks. Operation can be controlled with a combination of electronic hardware and software. The necessary drive electronics can be included on or off chip. In this way the ease of operation of these potentially powerful microinstruments is much simpler than most conventional analytical instruments, and more comparable to individual sensors.
In the area of instrumentation, microfabrication, micromachining, holds much promise for making small low-cost, fast-operating, portable, easy-to-operate systems for chemical analysis, clinical diagnostics and other applications. These microinstruments will rely on the integration of fluid-handling components.
Interest in microinstruments has been spurred by the need for improved chemical and biological analysis techniques in applications such as environmental remediation, chemical-warfare-agent detection and clinical diagnostics. For example, the DOE estimates that the superfund cleanup will require tens of millions of soil samples to be analyzed each year. The cost and manpower devoted to sample collection and analysis is exorbitant, and could be greatly reduced by using inexpensive, in-situ analyzers. However, the technology to make such analyzers is not available presently: existing sensors are very limited in their capabilities, and so-called portable analytical instruments are expensive and complicated to use.
Micromachining techniques of the nature disclosed in the present document allow the provision of analytical-instrument performance in microinstruments that are comparable in size, cost and ease-of-use to individual sensors. These same techniques can also be used to make disposable medical instruments such as DNA-based diagnostic tests, and miniature scientific instruments based on a number of technologies such as gas and liquid chromatography, electrophoresis, and flow-injection analysis. Several of these analysis techniques can be combined into a single chip to create very sophisticated systems that separate and analyze tiny samples without human intervention.
Essential for these microinstruments are suitable pump technologies to transport samples and reagents on the microscale. Many types of micromachined pumps have been developed recently. Most of these are discrete pumps, meaning that they operate by creating a pressure differential that drives fluids through the system in which they are functioning. The most common are silicon-based diaphragm pumps, which rely on electrostatic or thermo-pneumatic actuation to deflect a membrane that displaces fluid through one of two integrated check valves. Higher pump rates and higher pumping pressures have been achieved by actuating micromachined diaphragms with off-chip piezoelectric elements. These types of pumps are useful but have limitations. They are complicated to fabricate, subject to clogging, and pressure is generally limited by valve leakage. Discrete pump technologies also do not work well for moving fluids through microtunnels, i.e., through enclosed tunnels with cross-sectional dimensions of less than about 500 microns. This is because the pressure required to maintain a given flow rate increases extremely rapidly as the cross-sectional area of the tunnel is reduced.
Recently there has been much development of electroosmotic and electrophoretic pumps for liquid-based microinstruments. Electroosmosis is the movement of a liquid, under an applied electric field, in a fine tube or membrane. Electrophoresis is the movement of charged particles under an electric field in a liquid or gel. Electroosmosis and electrophoresis are very useful pumping mechanisms for liquid-based microinstruments. However, they do not work with gases, and are sensitive to the properties of the liquid such as conductivity and pH. Electroosmosis is also sensitive to the surface properties of the tunnel.
U.S. Pat. No. 5,006,749 to R. M. White describes methods for making an ultrasonic micromotor to move solids and briefly mentions the possibility of moving liquid droplets or streams. The method of this patent does not, however, describe a useful pump structure for moving fluids along an enclosed flow path, distributed pumping or chemical analysis instruments.
There is also recent work on fluid transport by acoustic streaming on a microscale. Acoustic streaming is steady fluid flow or pressure induced by high-intensity sound. It was first described by Faraday in 1831 and addressed theoretically by Rayleigh in 1884. Acoustic streaming fluid velocities are generally proportional to the square of the (mechanical) displacement of the driving source, and to the square of the acoustic displacement and velocity fields in the fluid. Acoustic streaming has been observed in fluids contacting vibrating cylinders, spheres, and plates.
Recently, steady-state pumping and localized stirring have been demonstrated with a micromachined flexural-plate-wave delay line. Pumping velocities as high as 30 mm/sec in air and 0.3 mm/sec in water have been observed.
The present inventors have shown as disclosed herein that a related structure can produce air flow rates of over 18 mm/sec in an enclosed tunnel 50 micrometers high, 500 micrometers wide and 8 mm long.
Acoustic streaming has also been generated with surface acoustic wave (SAWs). Shiokawa et al. have shown that water droplets can be ejected from the surface of a lithium niobate SAW delay line. This work does not, however, discuss structures that can move fluids in enclosed tunnels or in microsystems, or by distributed pumping.
Neither the White nor the Shiokawa et al. works describes a useful pump structure for moving fluids along an enclosed flow path, distributed pumping, or use with chemical-analysis instruments. Additionally, the flexural-wave structure has inherent limitations that prevent their use in forming a flexural-plate-wave pump or delay line from an enclosed narrow channel, that is, a channel with width less than about a wavelength. This is because in these configurations flexural-plate waves are generated via bimorph actuation using transducers that are uniform across the plate width. A composite plate is formed by laminating an actuation layer of a piezoelectric or electrostrictive material to one or more other layers. The center of flexure (neutral plane) of this plate is offset from the geometric center of the actuation layer. Flexural motion is produced when voltage is applied to the actuation layer, inducing a n in plane stress; since the neutral plane is offset from the center of the actuation layer, this stress causes the plate to flex. The entire area of the actuation layer under the applied voltage is driven into one in-plane stress state (compression or tension) causing the plate in that region to bend with one curvature (positive or negative). This mechanism works well when the plate width is large compared to the ultrasonic wavelength; however, when the plate is narrow compared to the wavelength and the plate edges are clamped (such as with the pump structure proposed wherein pumping is through a narrow tunnel) it is ineffective for producing flexural motion and flexural waves.
In the latter narrow geometry, the clamped plate edges have a large effect on the operation. For plate flexure to occur, the curvature of the plate at the midpoint between the edges must be opposite to that at the clamped edges. Bimorph construction with uniform transducers across the full width of the plate can not induce the opposite stress needed to produce these opposite curvatures, and thus is ineffective for producing flexural motion. Also, conversely, flexural motion and waves in this type of structure can not be detected effectively with a uniform transducer, because charge created piezoelectrically or electrostrictively near the edges of the plate will cancel that induced near the center, as these regions are in opposite states of curvature and stress. Furthermore, the boundaries make the generally less compliant to bending.
One of the first examples of a silicon-micromachined chemical-analysis system was a wafer-scale gas chromatograph developed by Terry et al. at Stanford University. The design was based on a conventional gas chromatograph (GC), which has five main components: (1) separation column, (2) detector, (3) sample injector, (4) column heater, and (5) bottled pressurized carrier gas. The pressurized carrier gas is attached to the inlet of the column and used to force gases through the column and into the detector on the end of the column. The sample injector typically employs a multiport valve between the bottled carrier gas and column to introduce a plug of sample gas into the carrier gas at the column inlet, which is under pressure. The sample is generally a mixture of known or unknown chemicals in different concentrations. After the sample plug is injected, it travels down the column with the carrier gas, and interacts with a coating on the interior walls of the column termed the stationary phase. This interaction causes the chemical components of the sample to be retained differentially, so that they become spatially separated as they travel down the column. The detector is generally a non-specific sensor that tells the presence or absence of a chemical. As the chemical components pass the detector, it outputs a series of peaks called a chromatogram. An individual chemical component is identified by its retention time. The column heater is needed stabilize column temperature so that retention times are predictable; additionally, it can be used to speed analysis times by temperature ramping.
Component identification is chromatography can also be aided by using multiple detectors that respond differently to a given set of chemicals. For example, using both a photoionization detector and a SAW sensor will yield more information than either detector alone. The mass spectrometer is another powerful analysis system that is used both alone and as a chromatographic detector; it separates and identifies chemicals by atomic mass. Microsized and microfabricated mass spectrometers are currently under development by Carl Friedhoff, et al at Northrup Grumman Corporation.
In conventional GCs, these components are all macroscopic in size; for example, the column is typically a coiled, fused-silica capillary around 10 meters in length. The resulting GC systems are bench-top-sized or larger with power requirements of hundreds or thousands of Watts.
Terry miniaturized a conventional GC by micromachining: the column was fabricated on a silicon wafer, to which individual silicon valves were attached for sample injection, and a thermal-conductivity detector for sample detection. This demonstrated that all of these components can be miniaturized by micromachining, with the exception of the bottled carrier gas.
Though innovative, the Terry GC did not perform as well as expected. The silicon-micromachined column had a non-round cross section unlike conventional fused-silica capillary columns and could not be coated evenly with a stationary phase, leading to poor performance or efficiency and resolution. Efficiency refers to the resolution of separation that can be achieved with a given length of column: A column with high efficiency separates and resolves chemicals in a shorter distance than a column with lower efficiency. The design did not provide any inherent advantages over a conventional GC in terms of manufacturing costs or performance, and the advantage of size reduction was negated by the need for bottled carrier gas. A company founded on this technology now produces portable gas chromatographs that use a few micromachined parts but still employ conventional fused-silica capillary columns and weigh several pounds.
Currently there is rapid development of liquid-phase microinstruments based on electroosmotic pumping. This technology has been used to create chip-based capillary-electrophoresis units with on-chip sample injection. Recently, a cyclic electrophoresis unit has been demonstrated. This demonstrates how micromachining can be used to produce devices that are not possible using conventional (i.e., fused-silica capillary) techniques.
In accordance with an embodiment of the invention a micro sized pump is set forth. It comprises a substrate which at least partially defines one or more walls of a longitudinally extending tunnel. The tunnel has a vibratable wall portion. An ultrasonic energy generator is positioned in ultrasonic energy transmitting relation to the vibratable wall portion. The ultrasonic energy generator is adapted to generate elastic waves which travel along the longitudinal extension of the tunnel. The pump is useful for moving material along the tunnel whereby chemical and biological analysis can be carried out on a micro scale.
Another embodiment of the invention is a chromatographic column comprising the pump as set forth above with walls of the tunnel being coated with a stationary phase.
Yet another embodiment of the invention is a chromatograph which includes the coated tunnel, a sample injector and one or more detectors; where appropriate a column heater is also provided.
Still another embodiment of the invention is an analysis system comprising the pump as set forth above in combination with any desired chemical analysis station with the pump being used to deliver a sample to be analyzed to the analysis station.
Attached hereto and incorporated herein by reference in its entirety is priority Provisional Patent Application Serial No. 60/009,665 filed Jan. 5, 1996 which includes still other embodiments of the invention.
The present invention uses ultrasonic waves to move gases, liquids and particulate solids within and along a tunnel by the physical phenomenon of acoustic streaming. Elastic waves traveling along the interface of a solid and a fluid produce intense sound in the fluid, causing it to move with some component of motion along the interface. The pump is formed with a tunnel that has elastic waves propagating along its wall thereby moving fluids longitudinally along the tunnel. The structure also has transducers which are used to generate the elastic waves.
This acoustic streaming pump is novel and has distinct advantages over other types of pumps, thereby enabling many applications in miniature/micro fluidic systems. In contrast to discrete pumps (such as diaphragm pumps) the mechanism that induces fluid motion (elastic wave motion) is distributed over the length of a flow tunnel. Furthermore, the elastic waves act on the fluid very close to the interface with the wall. The result is that the pump moves fluids down long shallow and narrow tunnels without incurring the pressure limitations of discrete pumps. The fabrication of this pump is also simple compared to most micropumps. It has no moving parts that are prone to mechanical failure. It is also distinctly different from the ultrasonic transport technologies described by White et al and the work of Shiokawa et al, which only move fluids on an open surface, or recirculate them in a well.
The present invention is also a significant departure from prior art as it describes structures and transducers that are effective for forming enclosed, narrow-channel acoustic pumps and sensors based on flexural plate waves as well as other types of ultrasonic waves.
The invention also includes microinstruments based on the pump.